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A First in Human Study of BAY2701439 to Look at Safety, How the Body Absorbs, Distributes and Excretes the Drug, and How Well the Drug Works in Participants With Advanced Cancer Expressing the HER2 Protein

NCT04147819

Description:

In this study, researchers want to learn about the safety of drug BAY2701439 and how well the drug works in patients with advanced cancer that has the protein HER2 (Human Epidermal growth factor Receptor 2) and cannot be cured by currently available treatment options. The study will include patients with HER2 expressing breast, gastric (stomach) or gastroesophageal (stomach and esophagus) cancer, as well as other cancers that have HER2. Researchers want to find the best dose of BAY2701439 for patients and look at the way the body absorbs, distributes and excretes the drug. The study drug is a type of therapy called a 'targeted alpha therapy' which uses an antibody to deliver a radioactive particle to cancer cells. BAY2701439 contains thorium-227 which emits radiation (a lot of energy that moves from one place to another with damaging effects). The thorium-227 in the drug is attached to an 'antibody' (large protein) that specifically binds to HER2 on the cancer cells and will emit its radiation in the form of alpha particles. The alpha particles are expected to damage the tumor cells and cause them to die, but spare surrounding tissue as alpha particles travel only very short distances in the body. This is the first study in humans for drug BAY2701439. Patients participating in this study will receive the drug by injection every 6 weeks a maximum 6 times. Observation after treatment last up to 3 years.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Not yet recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A First in Human Study of BAY2701439 to Look at Safety, How the Body Absorbs, Distributes and Excretes the Drug, and How Well the Drug Works in Participants With Advanced Cancer Expressing the HER2 Protein
  • Official Title: A Phase 1 Open-label, First-in-human, Multi-center Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Anti-tumor Activity of Thorium-227 Labeled Antibody-chelator Conjugate BAY2701439, in Participants With Advanced HER2-expressing Tumors

Clinical Trial IDs

  • ORG STUDY ID: 19829
  • SECONDARY ID: 2019-001741-40
  • NCT ID: NCT04147819

Conditions

  • Cancers With HER2 Expression

Interventions

DrugSynonymsArms
BAY2701439Dose escalation of BAY2701439
BAY2701438Dose escalation of BAY2701439

Purpose

In this study, researchers want to learn about the safety of drug BAY2701439 and how well the drug works in patients with advanced cancer that has the protein HER2 (Human Epidermal growth factor Receptor 2) and cannot be cured by currently available treatment options. The study will include patients with HER2 expressing breast, gastric (stomach) or gastroesophageal (stomach and esophagus) cancer, as well as other cancers that have HER2. Researchers want to find the best dose of BAY2701439 for patients and look at the way the body absorbs, distributes and excretes the drug. The study drug is a type of therapy called a 'targeted alpha therapy' which uses an antibody to deliver a radioactive particle to cancer cells. BAY2701439 contains thorium-227 which emits radiation (a lot of energy that moves from one place to another with damaging effects). The thorium-227 in the drug is attached to an 'antibody' (large protein) that specifically binds to HER2 on the cancer cells and will emit its radiation in the form of alpha particles. The alpha particles are expected to damage the tumor cells and cause them to die, but spare surrounding tissue as alpha particles travel only very short distances in the body. This is the first study in humans for drug BAY2701439. Patients participating in this study will receive the drug by injection every 6 weeks a maximum 6 times. Observation after treatment last up to 3 years.

Trial Arms

NameTypeDescriptionInterventions
Dose escalation of BAY2701439ExperimentalThe target population consists of participants with advanced HER2-expressing/amplified breast, gastric or gastroesophageal cancer.
  • BAY2701439
  • BAY2701438
HER2 overexpressing breast cancerExperimentalDose expansion of BAY2701439
  • BAY2701439
  • BAY2701438
HER2 low expressing breast cancerExperimentalDose expansion of BAY2701439
  • BAY2701439
  • BAY2701438
Other HER2 overexpressing advanced carcinomasExperimentalDose expansion of BAY2701439
  • BAY2701439
  • BAY2701438

Eligibility Criteria

        Inclusion Criteria:

          -  Male or female participants at least 18 years of age on the day of signing informed
             consent.

          -  Participants must meet the study phase-specific disease requirements:

        Dose escalation:

        Pathologically documented, HER2-expressing (IHC3+, 2+, or 1+ and/or ISH+), unresectable
        locally advanced or metastatic gastric, gastroesophageal, or breast cancer that has
        relapsed after standard treatment options, or for which no standard treatment is available.
        Participants with gastric or gastroesophageal cancer must not have had prior radiotherapy.
        Participants in the dose escalation cohorts must have evaluable disease by RECIST 1.1,
        assessed by local imaging.

        - Dose expansion: Group A: Pathologically documented unresectable, locally advanced or
        metastatic breast cancer with HER2 overexpression or amplification (IHC3+ or IHC2+/ISH+)
        that has relapsed that has relapsed after standard treatment options, or for which no
        standard treatment is available.

        Group B: Pathologically documented unresectable locally advanced or metastatic breast
        cancer with HER2 low expression (IHC2+/ISH-, IHC1+/ISH-, or IHC1+/ISH untested) that has
        relapsed after standard treatment options, or for which no standard treatment is available.

        Group C: Pathologically documented, unresectable locally advanced or metastatic carcinomas
        other than breast cancer with HER2 overexpression or amplification/mutation (IHC3+ or
        IHC2+/ISH+), that has relapsed after standard treatment options or for which no standard
        treatment is available.

        Participants in the dose expansion cohorts must have measurable disease by RECIST 1.1,
        assessed by local imaging.

          -  Availability of fresh or archival tumor samples - archival tumor samples obtained
             after disease progression on the most recent anti-cancer treatment may be accepted;
             those obtained prior to the last anti-cancer treatment may be accepted, upon agreement
             between the Sponsor and the Investigator.

          -  Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1.

          -  Life expectancy of at least 6 months, as estimated by the Investigator.

          -  Adequate bone marrow, hepatic, and renal function, as assessed by the following
             laboratory requirements, to be conducted within 28 days before start of BAY2701439
             administration:

               -  Hemoglobin ≥ 9.0 g/dL

               -  Absolute neutrophil count (ANC) ≥ 1500/mm*3

               -  Platelet count ≥ 100,000/mm*3

               -  Total bilirubin ≤ 1.5 X the upper limit of normal (ULN), except if confirmed
                  history of Gilbert's disease

               -  Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST) ˂ 2.5 x ULN
                  (≤ 5 x ULN for participants with liver involvement)

               -  Participants on a stable dose of anti-coagulation therapy will be allowed to
                  participate if they have no sign of bleeding or clotting, and Prothrombin
                  time/International normalized ratio (PT/INR) and aPTT test results are compatible
                  with the acceptable benefit-risk ratio at the Investigator's discretion

               -  Serum creatinine ≤ 1.5 x ULN and glomerular filtration rate (GFR)≥ 45 mL/min/1.73
                  m*2, according to the Modified Diet in Renal Disease (MDRD)abbreviated formula.

          -  A negative serum pregnancy test in women of childbearing potential (WOCBP) performed
             within 7 days before the start of BAY2701439 administration. Women and men of
             reproductive potential must agree to use highly effective methods of contraception,
             when sexually active, during the time period between signing the informed consent form
             until at least 6 months after the last administration of BAY2701439.

          -  Male and/or female who meet the requirements for contraception and breastfeeding as
             follows:

        Male participants: A male participant must agree to use highly effective contraception
        during the intervention period and for at least 6 months after intervention and refrain
        from donating sperm during this period.

        Female participants: A female participant is eligible to participate if she is not pregnant
        (confirmed by a negative serum pregnancy test within 7 days of first study treatment), not
        breastfeeding, or is not a woman of childbearing potential.

        Women of childbearing potential (WOCBP) must agree to use highly effective contraception
        during the intervention period and for at least 6 months after the last dose of study
        treatment.

        Contraceptive use by men or women should be consistent with local regulations regarding the
        methods of contraception for those participating in clinical studies.

        - Capable of giving signed informed consent which includes compliance with the requirements
        and restrictions listed in the informed consent form (ICF) and in this protocol

        Exclusion Criteria:

          -  Impaired cardiac function or clinically significant cardiac disease (i.e. congestive
             heart failure (CHF) New York Heart Association (NYHA) Class II, III or IV).

          -  Left ventricular ejection fraction (LVEF) < 50% (as measured at screening by
             echocardiogram).

          -  History or concurrent condition of interstitial lung disease/pneumonitis or severely
             impaired pulmonary function.

          -  Participants known to be affected by genetic defects linked to radiation
             hypersensitivity, such as ataxia-telangiectasia (A-T; Online Mendelian Inheritance in
             Man [OMIM] #208900) and A-T-like disorder (meiotic recombination 11 homolog [MRE11]),
             Nijmegen breakage syndrome (OMIM #251260) and Nijmegen breakage Syndrome-like disorder
             (RAD50), Fanconi anemia (OMIM #227650), DNA ligase IV deficiency (OMIM #606593),
             RIDDLE syndrome (RNF168), radiosensitive severe combined immunodeficiency (RS-SCID),
             DNA-PK radiosensitive combined immunodeficiency (DNA-PK-RS-SCID), Cornelia de Lange
             syndrome.

          -  History of Myelodysplastic syndrome (MDS)/treatment-related acute myeloid leukemia
             (t-AML) or with features suggestive of MDS/AML.

          -  Infections of Common terminology criteria for adverse events (CTCAE) version 5.0 Grade
             2 not responding to therapy or active clinically serious infections of CTCAE Grade >2.

          -  History of hypersensitivity or severe infusion related reaction to any
             Trastuzumab-containing drug (e.g. trastuzumab, T-DM1) or any other ingredients
             contained in BAY2701439.

          -  Chemotherapy, experimental cancer therapy, biologic therapy or immunotherapy within 4
             weeks before start of BAY2701439 administration. Start of study treatment is allowed
             in shorter timeframes provided 5 half-lives of the prior drug(s) have elapsed before
             the start of BAY2701439 administration. Previous high-dose chemotherapy needing
             hematopoietic-stem-cell-rescue is prohibited.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Dose escalation: Incidence of TEAEs including TESAEs
Time Frame:After first administration of study intervention up to 42 days after the last dose of study intervention
Safety Issue:
Description:TEAE: Treatment-emergent adverse event TESAE: Treatment-emergent serious adverse event

Secondary Outcome Measures

Measure:Dose escalation: Recommended dose level(s) of BAY2701439 for the dose expansion cohorts
Time Frame:Maximum 6 cycles (each cycle is 42 days)
Safety Issue:
Description:The dose level(s) recommended for the dose expansion cohorts will be defined after evaluation of incidence and severity of TEAEs, PK, and ORR by RECIST 1.1, collected in the cycles of treatment during the dose escalation part of the study.
Measure:Dose escalation: Recommended treatment schedule of BAY2701439 for the dose expansion cohorts
Time Frame:Maximum 6 cycles (each cycle is 42 days)
Safety Issue:
Description:The treatment schedule recommended for the dose expansion cohorts will be defined after evaluation of incidence and severity of TEAEs, PK, and ORR by RECIST 1.1, collected in the cycles of treatment during the dose escalation part of the study.
Measure:Dose expansion: Recommended dose for further clinical development of BAY2701439
Time Frame:Maximum 6 cycles (each cycle is 42 days)
Safety Issue:
Description:The dose recommended for further clinical development will be defined after evaluation of incidence and severity of TEAEs, PK, and ORR by RECIST 1.1, collected in the cycles of treatment during the dose escalation and expansion parts of the study.
Measure:Cmax of thorium-227
Time Frame:Cycle 1 (42 days)
Safety Issue:
Description:Cmax: Maximum observed exposure
Measure:Cmax of radium-223
Time Frame:Cycle 1 (42 days)
Safety Issue:
Description:Cmax: Maximum observed exposure
Measure:Cmax of total antibody
Time Frame:Cycle 1 (42 days)
Safety Issue:
Description:Cmax: Maximum observed exposure
Measure:AUC(0-42 days) of thorium-227
Time Frame:Cycle 1 (42 days)
Safety Issue:
Description:AUC: Area under the curve
Measure:AUC(0-42 days) of radium-223
Time Frame:Cycle 1 (42 days)
Safety Issue:
Description:AUC: Area under the curve
Measure:AUC(0-42 days) of total antibody
Time Frame:Cycle 1 (42 days)
Safety Issue:
Description:AUC: Area under the curve

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Bayer

Trial Keywords

  • Human epidermal growth factor receptor 2(HER2)
  • Targeted alpha therapy
  • Thorium-227

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